Nucleic acid-based and protein-based therapeutic agents represent promising new drugs for the treatment of various diseases and disorders including cancer, infectious diseases, neurological disorders, inflammation and immune disorders, and cardiovascular disease. However, many proposed nucleic acid-based and protein-based therapeutic agents have not been successful because of a limited ability for these agents to reach the target tissue and exert a therapeutic effect. The challenges in developing effective nucleic acid-based and protein-based therapeutic agents include degradation, rapid clearance through the kidneys, short-half lives, low stability, the generation of neutralizing antibodies to the foreign antigen, and rapid clearance of these therapeutic agents from the immune system. Efforts to increase efficacy of these therapeutics have included chemical modifications, e.g., pegylation of proteins and phosphorothioate modifications of nucleic acids. Such chemical modifications improve stability, increase half-lives, and decrease the likelihood of triggering an immune response. However, the success of these chemical modifications in improving therapeutic efficacy is dependent on the drug, e.g., the nucleic acid sequence, and can vary depending on the route of drug delivery.
As such, there is an on-going need for nucleic acid-based and protein-based therapeutics that are long-lasting and provide effective treatment for diseases and disorders.